Lung cancer is a malignant tumor that starts in the bronchi or alveoli, and is known as the leading cause of death from malignant tumors. Lung cancer is classified roughly into two types: small-cell lung carcinoma; and non-small-cell lung carcinoma. The non-small-cell lung carcinoma is further classified into three types: adenocarcinoma; squamous-cell carcinoma; and large-cell carcinoma. For screening for lung cancer, chest X-ray and sputum cytology are used. However, it is difficult to find lesions located at sites overlapped with the heart or bones and small lesions by using chest X-ray. The sputum cytology is a test that detects cancer cells in sputum derived from cancerous tissues, but it is difficult to find the cancer cells by only one test and thus multiple tests over several days are necessary. This imposes a large burden on subjects.
For screening for lung cancer, measurement of tumor markers in blood is also performed. The markers for small-cell lung carcinoma to be used are pro-gastrin releasing peptide (ProGRP) and neuron specific enolase (NSE). The markers for lung squamous-cell carcinoma to be used are squamous cell carcinoma antigen (SCC antigen) and cytokeratin 19 fragments (CYFRA). The markers for lung adenocarcinoma to be used are carcinoembryonic antigen (CEA) and sialyl Lewis X-I antigen (SLX). However, these tumor markers have insufficient sensitivity in detecting cancer, and include markers used for cancers of different types from lung cancer.
Meanwhile, new methods for diagnosing cancer based on genetic information have been studied in recent years. The methods include, for example, a method based on information on methylation of DNA. In this method, CpG sites (5′-(CG)-3′) in base sequences of certain genes are used as markers. Then, information such as the presence or absence of cancer cells is obtained based on the analysis results of the methylation status of the markers, and is used as an index for diagnosis of cancer.
Methods for determining cancer by DNA methylation analysis have been studied and developed for lung cancer. For example, the publication by Rauch T. et al. discloses that CpG islands of HOXA7 and HOXA9 genes are highly methylated frequently in tissues from stage I lung squamous cell carcinoma (see Rauch T. et al., Proc. Natl. Acad. Sci. USA, vol. 104, p. 5527-5532 (2007)). US 2012/0202202 A discloses a method for detecting various types of cancer including lung cancer by measuring methylation levels in CpG islands of HOXA6, HOXA7, and HOXA9 genes.
Although genes with abnormal methylation in lung cancer have been reported as described above, the number of genes used as markers for detecting lung cancer is few. Thus, there is a demand for development of novel markers for detecting lung cancer using methylation analysis of genes.